rs12663916

Variant names:

• chr6-64591961-G-A
• rs12663916
• NM_001142800.2:c.3906C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-64591961-G-A
• chr6-64591961-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142800.2(EYS):​c.3906C>T​(p.His1302His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,499,362 control chromosomes in the GnomAD database, including 13,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (928 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12257 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.0400
• Publications: 8 publications found

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-64591961-G-A is Benign according to our data. Variant chr6-64591961-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.3906C>T	p.His1302His	synonymous	Exon 26 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.3906C>T	p.His1302His	synonymous	Exon 26 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.3906C>T	p.His1302His	synonymous	Exon 26 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.3906C>T	p.His1302His	synonymous	Exon 26 of 44	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15357 AN: 151978 Hom.: 931 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0995

GnomAD2 exomes AF: 0.109 AC: 13505 AN: 124052 AF XY: 0.109

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0738

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.129 AC: 173779 AN: 1347266 Hom.: 12257 Cov.: 34 AF XY: 0.129 AC XY: 84760 AN XY: 659530

African (AFR) AF: 0.0289 AC: 865 AN: 29962

American (AMR) AF: 0.120 AC: 3488 AN: 29122

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 1728 AN: 22974

East Asian (EAS) AF: 0.144 AC: 5045 AN: 35086

South Asian (SAS) AF: 0.0984 AC: 7119 AN: 72344

European-Finnish (FIN) AF: 0.0786 AC: 3758 AN: 47786

Middle Eastern (MID) AF: 0.0548 AC: 300 AN: 5470

European-Non Finnish (NFE) AF: 0.138 AC: 144687 AN: 1048804

Other (OTH) AF: 0.122 AC: 6789 AN: 55718

GnomAD4 genome AF: 0.101 AC: 15352 AN: 152096 Hom.: 928 Cov.: 32 AF XY: 0.0993 AC XY: 7383 AN XY: 74362

African (AFR) AF: 0.0364 AC: 1510 AN: 41522

American (AMR) AF: 0.125 AC: 1905 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.166 AC: 855 AN: 5146

South Asian (SAS) AF: 0.113 AC: 543 AN: 4826

European-Finnish (FIN) AF: 0.0739 AC: 783 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9181 AN: 67962

Other (OTH) AF: 0.0985 AC: 208 AN: 2112

Alfa AF: 0.0709 Hom.: 126

Bravo AF: 0.105

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Retinitis pigmentosa (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.33
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12663916; hg19: chr6-65301854; COSMIC: COSV108153304; COSMIC: COSV108153304;